Method for Pulmonary Administration Using Negative Pressure Generated by Inspiration in Mice

Abstract

When developing inhaled medicines for respiratory diseases, such as chronic obstructive pulmonary disease, drugs need to be administered by pulmonary delivery to animals in non-clinical tests. Common methods require application of pressure during administration, and it may cause lung injury, so we focused on the inhalation of liquid medicines by mice themselves. This study aimed to evaluate a negative pressure method of pulmonary administration in mice by self-inhalation. First, to confirm the accuracy of delivery of liquid medicines into lungs and the potential for lung injury, Institute of Cancer Research (ICR) mice received methylene blue tetrahydrate or saline by the negative pressure method. We assessed drug distribution and usefulness of this method by administering porcine pancreatic elastase and all-trans-retinoic acid (ATRA) to mice. Consequently, we confirmed good distribution of the dye and no injury such as disruption of blood flow or destruction of alveoli in lungs of mice. Following production of the murine emphysema model, the mean linear intercept (Lm) was calculated as 78 ± 4 μm. Moreover, a significant therapeutic effect of administration of the ATRA was confirmed. These results suggest that this negative pressure method of administration may be useful for pulmonary administration in non-clinical tests.

Am80-Encapsulated Lipid Nanoparticles, Developed with the Aim of Achieving Alveolar Regeneration, Have an Improvement Effect on Pulmonary Emphysema

“…The drug solution administered by our pulmonary administration method is distributed throughout the lung, including the alveolar region [ 33 , 34 ]. In addition, pulmonary administration of Am80 by our method to elastase-induced COPD model mice results in alveolar repair [ 21 ].…”

“…The pulmonary administration used in this study was the negative-pressure method that we previously established [ 34 ]. It was carried out with a stainless-steel oral sonde for oral administration (N-PK 002, Nihon Bioresearch Inc., Nagoya, Japan), which is equivalent in diameter to the mouse airway.…”

Intracellular Drug Delivery Process of Am80-Encapsulated Lipid Nanoparticles Aiming for Alveolar Regeneration

“…We previously reported the pulmonary administration method used [ 37 ]. Mice were anesthetized with isoflurane (MSD Animal Health K.K, Osaka, Japan) and held in a Mouse Intubation Platform-Model MIP (Penn-Century, Wyndmoor, PA, USA).…”